This program of investigation focuses on the genetics and epigenetics of Specific Language Impairment (SLI). We investigate longitudinal behavioral language phenotypes within a multi-gene developmental model involving a complex interaction of genetics, developmental brain changes, and overlapping phenotypes that intertwine throughout childhood with enduring individual differences in performance levels. Four previous award cycles have generated an ongoing empirical archive of proband and family data that is unique for the detailed documentation of longitudinal growth patterns across multiple indices of language, non-word repetition and other verbal memory tasks, reading, and speech sound acquisition. The ongoing longitudinal study documents a consistent picture for children with SLI of delayed onset of language, lower language levels that persist through adolescence, parallel growth trajectories to unaffected children although at lower levels of performance, and grammatical limitations out of sync with other dimensions of language although also following the growth trajectories of unaffected children. Family members show an elevated rate of affectedness. Language and reading impairments are co-morbid in affected children. Candidate gene linkage and association outcomes suggest gene influences for language, speech, and reading impairments in a set of genes known to influence CNS development. The behavioral growth phenotypes suggest maturational mechanisms as unexamined components of potential genetic influence and the genetics analyses point toward CNS development. What is missing is information about brain maturation in children with and without SLI in this well documented longitudinal sample. The specific aims of this proposal continue the first two aims from the current funding cycle, revise the third aim, and add a fourth aim to expand the scope to include brain imaging of language processing in children with SLI: (1) To compile a behavioral database of child probands, control children, and family members to be used for developing growth phenotypes in language, reading, speech, and non-word repetition. (2) To investigate the relationships among grammatical markers, vocabulary, omnibus language tests, verbal memory, reading and nonverbal intelligence measures in children with SLI and control children and how the relationships change over time. (3) Identify networks of genes involved in the development of CNS structures and functions involved in language impairment. (4) To characterize brain functional neuroanatomy for language processing in children with and without SLI, including evaluation of brain maturation indices. Collectively the proposed aims of this program of investigation are to identify potential brain phenotypes as biomarkers that are active on the causal pathway of SLI and that could link the DNA variants with the behavioral growth linguistic phenotypes and related endophenotypes. The outcomes would have implications for clinical interventions in the areas of speech, language, and reading impairments and in disabilities associated with language impairments such as autism and intellectual impairments.